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Epigenetic Changes in Neurodegenerative Diseases

  • Kwon, Min Jee;Kim, Sunhong;Han, Myeong Hoon;Lee, Sung Bae
    • Molecules and Cells
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    • v.39 no.11
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    • pp.783-789
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    • 2016
  • Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer's disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

Shedding; towards a new paradigm of syndecan function in cancer

  • Choi, So-Joong;Lee, Ha-Won;Choi, Jung-Ran;Oh, Eok-Soo
    • BMB Reports
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    • v.43 no.5
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    • pp.305-310
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    • 2010
  • Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors. Whether these remaining cleavage products are still capable of functioning as cell surface receptors to efficiently transduce signals inside of cells is not clear. However, shedding transforms cell surface receptor syndecans into soluble forms, which, like growth factors, may act as novel ligands to induce cellular responses by association with other cell surface receptors. It is becoming interestingly evident that shed syndecans also contribute significantly to syndecan functions in cancer biology. This review presents current knowledge about syndecan shedding and its functional significance, particularly in the context of cancer.

Constraining the Mass Loss Geometry of Beta Lyrae

  • Lomax, Jamie R.
    • Journal of Astronomy and Space Sciences
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    • v.29 no.1
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    • pp.47-49
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    • 2012
  • Massive binary stars lose mass by two mechanisms: jet-driven mass loss during periods of active mass transfer and by wind-driven mass loss. Beta Lyrae is an eclipsing, semi-detached binary whose state of active mass transfer provides a unique opportunity to study how the evolution of binary systems is affected by jet-driven mass loss. Roche lobe overflow from the primary star feeds the thick accretion disk which almost completely obscures the mass-gaining star. A hot spot predicted to be on the edge of the accretion disk may be the source of beta Lyrae's bipolar outflows. I present results from spectropolarimetric data taken with the University of Wisconsin's Half-Wave Spectropolarimeter and the Flower and Cook Observatory's photoelastic modulating polarimeter instrument which have implications for our current understanding of the system's disk geometry. Using broadband polarimetric analysis, I derive new information about the structure of the disk and the presence and location of a hot spot. These results place constraints on the geometrical distribution of material in beta Lyrae and can help quantify the amount of mass lost from massive interacting binary systems during phases of mass transfer and jet-driven mass loss.

A Possibility of Modulating the Geomagnetic Field by the Solar Eclipse

  • Kim, Jung-Hee;Chang, Heon-Young
    • The Bulletin of The Korean Astronomical Society
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    • v.41 no.2
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    • pp.68.1-68.1
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    • 2016
  • The solar eclipse affects terrestrial environments in various aspects. For instance, it is well known that the electron concentration and current density decrease in the ionosphere due to the reduction of solar irradiation during solar eclipse. In this study, we carry out the statistical analysis of x, y, z, H-components, and the intensity of the geomagnetic field using the ground based geomagnetic data observed during the solar eclipses from 1991 to 2016. First, we confirm that characteristic decreases in the x and H-components can be seen in the vicinity of the maximum eclipse time at the observing site. Second, we find that the decrease in x and H-components is more conspicuous during the total solar eclipse rather than the partial or annular eclipses. We also find that such a dip is likely to be noticed when the observing site locates in the second half compared to the first half of the eclipse path, as well as when the eclipse occurs in dusk side than in dawn side. Third, we find that reductions in the ground geomagnetic field by the solar eclipse are more evident in the ascending phase of the solar cycle than in the descending phase. Finally, we briefly discuss implications of our findings.

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Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases

  • Kang, Chanhee
    • Molecules and Cells
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    • v.42 no.12
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    • pp.821-827
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    • 2019
  • Aging is the most important single risk factor for many chronic diseases such as cancer, metabolic syndrome, and neurodegenerative disorders. Targeting aging itself might, therefore, be a better strategy than targeting each chronic disease individually for enhancing human health. Although much should be achieved for completely understanding the biological basis of aging, cellular senescence is now believed to mainly contribute to organismal aging via two independent, yet not mutually exclusive mechanisms: on the one hand, senescence of stem cells leads to exhaustion of stem cells and thus decreases tissue regeneration. On the other hand, senescent cells secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, collectively termed as the senescence-associated secretory phenotype (SASP), which causes chronic inflammation and tissue dysfunction. Much effort has been recently made to therapeutically target detrimental effects of cellular senescence including selectively eliminating senescent cells (senolytics) and modulating a proinflammatory senescent secretome (senostatics). Here, we discuss current progress and limitations in understanding molecular mechanisms of senolytics and senostatics and therapeutic strategies for applying them. Furthermore, we propose how these novel interventions for aging treatment could be improved, based on lessons learned from cancer treatment.

Shengmaisan Regulates Pacemaker Potentials in Interstitial Cells of Cajal in Mice

  • Kim, Byung Joo
    • Journal of Pharmacopuncture
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    • v.16 no.4
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    • pp.36-42
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    • 2013
  • Objectives: Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of diverse organs in Korea. The interstitial cells of Cajal (ICCs) are pacemaker cells that play an important role in the generation of coordinated gastrointestinal (GI) motility. We have aimed to investigate the effects of SMS in the ICCs in the mouse small intestine. Methods: To dissociate the ICCs, we used enzymatic digestions from the small intestine in a mouse. After that, the ICCs were identified immunologically by using the anti-c-kit antibody. In the ICCs, the electrophysiological whole-cell patch-clamp configuration was used to record pacemaker potentials in the cultured ICCs. Results: The ICCs generated pacemaker potentials in the mouse small intestine. SMS produced membrane depolarization with concentration-dependent manners in the current clamp mode. Pretreatment with a $Ca^{2+}$ free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, stopped the generation of the pacemaker potentials. In the case of $Ca^{2+}$-free solutions, SMS induced membrane depolarizations. However, when thapsigargin in a bath solution was applied, the membrane depolarization was not produced by SMS. The membrane depolarizations produced by SMS were inhibited by U-73122, an active phospholipase C (PLC) inhibitors. Furthermore, chelerythrine and calphostin C, a protein kinase C (PKC) inhibitors had no effects on SMS-induced membrane depolarizations. Conclusions: These results suggest that SMS might affect GI motility by modulating the pacemaker activity through an internal $Ca^{2+}$- and PLC-dependent and PKC-independent pathway in the ICCs.

A review of pathophysiological mechanism of Bisphosphonate-related osteonecrosis of the jaw (임상가를 위한 특집 1 - 비스포스포네이트 관련 골괴사의 병태생리학적 기전에 대한 검토)

  • Kwon, Tae-Geon
    • The Journal of the Korean dental association
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    • v.52 no.4
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    • pp.192-202
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    • 2014
  • Bisphosphonate(BP) significantly influence the hone remodeling process. Increasing number of patients with osteoporosis and metastatic bone disease need high dose or long term bisphosphonate therapy. Major adverse effect is jaw bone necrosis and now the bisphosphonate-related necrosis of the jaw(BRONJ) is the major concern of dental practitioner. This study intended to perform the review of the current understandings concerning the pathophysiology of BRONJ. Even though pathophysiological mechanism of BRONJ is not clearly elucidated but now suggested as largely two different concepts; so-called "inside-out" or "outside-in" theory. Inside-out theory emphasize the osteonecrosis of the jaw is the initial major event and subsequent infection and inflammation is the second event that accompanies bone exposure and death of overlying mucosa. However, in "outside-in" theory, infection or inflammation initiated by traumatized oral epithelium is the major event of BRONJ. Both theory would be partially explain BRONJ. Recent research reveals the immune modulating effect and influence of microcrack accumulation by BP. These findings and those of others might explain the missing part of outside-in theory.

Calculation of UWB Communication System Capacity with Timing litter (타이밍 지터를 고려한 UWB 통신 시스템 용량 계산)

  • 박장우
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.8 no.4
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    • pp.767-773
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    • 2004
  • An UWB communication system are a promising communication technique suitable for the current trends, which are requesting communication methods with the high throughputs and very high speed. A key feature of UWB communication systems is the very narrow pulse used in transmitting the data and PPM(Pulse Position Modulation) for modulating the data. So, the timing accuracy is very important. It is very important to accurately analyze the effect of the timing jitter on the performance of UWB communication systems. In this paper, the methods of analyzing the timing jitter effects on UWB communication systems are introduced. In particular, the channel capacities with timing jitter are calculated including the multiuser access interference.

Modulated Pulse Power Sputtering Technology for Deposition of Al Doped ZnO Thin Film (Al doped ZnO 박막 증착을 위한 모듈레이티드 펄스 스퍼터링)

  • Yang, Won-Kyun;Joo, Jung-Hoon
    • Journal of the Korean institute of surface engineering
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    • v.45 no.2
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    • pp.53-60
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    • 2012
  • Modulated Pulse Power (MPP) magnetron sputtering is a new high-power pulsed magnetron sputtering (HPPMS) technology which overcomes the low deposition rate problem by modulating the pulse voltage shape, amplitude, and the duration. Highly ionized magnetron sputtering can be performed without arcing because it can be controlled as multiple steps of micro pulses within one overall pulse period in the range of 500-3,000 ${\mu}s$. In this study, the various waveforms of discharge voltage and current for micro pulse sets of MPP were investigated to find the possibility of controlling the strongly ionized plasma mode. Enhanced ionization of the sputtered metal atoms was obtained by OES. Large grained columnar structure can be grown by the strongly ionized plasma mode in the AZO deposition using MPP. In the most highly ionized deposition condition, the preferred orientation of (002) plane decreased, and the resistivity, therefore, increased by the plasma damage.

Four-Week Repeated Oral Toxicity Study of AIP1, a Water-soluble Carbohydrate Fraction from Artemisia iwayomogi in Mice

  • Ryu, Sung-Ha;Jo, Hae-Ran;Kim, Ji-Won;Youn, Hyun-Joo;Kim, Kyu-Bong
    • Toxicological Research
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    • v.27 no.4
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    • pp.261-267
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    • 2011
  • Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.